Outcomes Associated with the Off-label Use of Medical Devices in Congenital Heart Disease at a Single Institute

BACKGROUND AND OBJECTIVES: While the off-label use of implantable medical devices for treating congenital heart disease is not uncommon, the present conditions and outcomes of their off-label use have rarely been described. Therefore, this study evaluated the prevalence and results of using implantable devices off-label to treat congenital heart disease at a single institute. SUBJECTS AND METHODS: This was a retrospective study based on the medical records of catheter-based interventions for congenital heart disease performed from July 1, 1995 to June 1, 2015. The inclusion criterion was the off-label use of an implantable device. Patient demographic data, procedural success, and follow-up status regarding late complications were investigated, and the results of the off-label use of each device were compared. RESULTS: Off-label use occurred in 144 of 1730 interventions with device implantation, accounting for 8.3% of the interventions. The median patient age and mean body weight were 51.0 months and 16.3 kg, respectively. Immediate and late failures were found in 9 cases, and 3 cases of mortality were not directly related to the devices used. The overall success rate was 93.8%. There were no long-term complications of the off-label use of occlusion devices. No procedural failures resulted from stent implantation, but one case of stent malposition and two cases of stent fracture were identified after procedure completion. CONCLUSION: In general, the off-label use of implantable devices for treating congenital heart disease is safe and effective.

How Long Can the Next Intervention Be Delayed after Balloon Dilatation of Homograft in the Pulmonary Position?

BACKGROUND AND OBJECTIVES: We investigated the effectiveness of balloon dilatation of homograft conduits in the pulmonary position in delaying surgical replacement. SUBJECTS AND METHODS: We reviewed the medical records of patients who underwent balloon dilatation of their homograft in the pulmonary position from 2001 to 2015. The pressure gradient and ratio of right ventricular pressure were measured before and after the procedure. The primary goal of this study was to evaluate the parameters associated with the interval to next surgical or catheter intervention. RESULTS: Twenty-eight balloon dilations were performed in 26 patients. The median ages of patients with homograft insertion and balloon dilatation were 20.3 months and 4.5 years, respectively. The origins of the homografts were the aorta (53.6%), pulmonary artery (32.1%), and femoral vein (14.3%). The median interval after conduit implantation was 26.7 months. The mean ratio of balloon to graft size was 0.87. The pressure gradient through the homograft and the ratio of right ventricle to aorta pressure were significantly improved after balloon dilatation (p<0.001). There were no adverse events during the procedure with the exception of one case of balloon rupture. The median interval to next intervention was 12.9 months. The median interval of freedom from re-intervention was 16.6 months. Cox proportional hazards analysis revealed that the interval of freedom from re-intervention differed only according to origin of the homograft (p=0.032), with the pulmonary artery having the longest interval of freedom from re-intervention (p=0.043). CONCLUSION: Balloon dilatation of homografts in the pulmonary position can be safely performed, and homografts of the pulmonary artery are associated with a longer interval to re-intervention.

Disease-specific induced pluripotent stem cells: a platform for human disease modeling and drug discovery

The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss the previously established childhood cerebral adrenoleukodystrophy (CCALD)- and adrenomyeloneuropathy (AMN)-iPSCs by our group. Through DNA fingerprinting analysis, the origins of generated disease-specific iPSC lines were identified. Each iPSC line exhibited an intense alkaline phosphatase activity, expression of pluripotent markers, and the potential to differentiate into all three embryonic germ layers: the ectoderm, endoderm, and mesoderm. Expression of endogenous pluripotent markers and downregulation of retrovirus-delivered transgenes [OCT4 (POU5F1), SOX2, KLF4, and c-MYC] were observed in the generated iPSCs. Collectively, our results demonstrated that disease-specific iPSC lines characteristically resembled hESC lines. Furthermore, we were able to differentiate PD-iPSCs, one of the disease-specific-iPSC lines we generated, into dopaminergic (DA) neurons, the cell type mostly affected by PD. These PD-specific DA neurons along with other examples of cell models derived from disease-specific iPSCs would provide a powerful platform for examining the pathophysiology of relevant diseases at the cellular and molecular levels and for developing new drugs and therapeutic regimens.

A Survey of Patients' Thoughts on Anesthesia and Anesthesiologists following Experience with Anesthesia / 대한마취과학회지

BACKGROUND: The image and status of anesthesiology as a medical specialty in the eyes of the general public has been a problem. This study assessed the patients' thoughts on anesthesiologists and their preoperative concerns and examined the influence of any previous anesthetic experience on their apprehension. METHODS: One hundred thirty-nine patients undergoing elective surgical procedures were surveyed with a questionnaire regarding their thoughts on anesthesiologists and their preoperative concerns at preoperative visits. The results were analyzed in terms of a previous experience with anesthesia. RESULTS: Sixty-five patients had previous experience with anesthesia (Group 1), and 74 patients had none (Group 2). Seventy-one percent of patients in Group 1 and 80% in Group 2 reported that a physician-anesthesiologist was in charge of their anesthesia. Regarding the responsibility for the patients' safety during the surgical procedures, 83% of patients in Group 1 and 82% in Group 2 reported that the anesthesiologists were responsible for the patients' well-being. Fifty-seven percent of patients in Group 1 and 58% in Group 2 reported that the anesthesiologists were responsible for their safe recovery from the anesthesia. The most frequent preoperative apprehensions were postoperative pain (57% in Group 1 and 62% in Group 2) and the risk of not waking up from the anesthesia (60% in Group 1 and 57% in Group 2). There were no significant differences between the two groups. CONCLUSIONS: Passive learning from previous anesthetic experience does not affect the patients' thoughts on the anesthesiologists and their preoperative concerns.

Medial Pedicle Vertical Reduction Mammoplasty

Most recent breast reduction techniques tend to get natural cone shaped breast with minimal scar. On this purpose, we have performed 7 cases of vertical reduction mammoplasty with medial pedicle from August 2003 to August 2005. The mean age of patient was 29, and the average resection amount was 760 gram per breast. The most of the patient were satisfied with their postoperative size, shape and scar. As compared with classical superior pedicle vertical reduction mammoplasty, by using medial pedicle, this technique could use short and wide-ranging pedicle, avoid skin undermining, evade exposure of pectoralis major fascia and remove the fixation as well. And this technique did not operate liposuction. As descrived above, the advantages of vertical mammoplasty using a medial pedicle are as follows: 1. Limited postoperative scar of incision. 2. More effective preservation of sensation to the nipple-areolar complex and physiological function as breast feeding. 3. More aesthetic shape of breast. 4. The procedure is easy to perform. 5. Shortening the period of postoperative care.

The Effect of Placenta Extract on Proliferation and Differentiation of Human Chondrocytes

PURPOSE: The isolated human chondrocytes for cartilage reconstruction and transplantation presents a major problem as these cells would change biologically in vitro. For more effective applications of these cells in the clinical field, it is necessary to get a large amount of cells in a short period without affecting their function and phenotype. METHODS: This study reports the effects of placenta extract on chondrocytes in vitro. We initiated this study on the basis of the hypothesis that placenta extract can influence both the proliferation of chondrocytes and their biologic functions(for example, to express cell specific gene or to produce their own extracellular matrix). Chondrocytes in monolayer culture with or without placenta extract were collected and analyzed by MTT assay, ECM assay, and RT-PCR. RESULTS: Placenta extract stimulated the proliferation of chondrocytes in monolayer culture. The phenotype of chondrocytes was well maintained during the expansion in monolayers. Chondrocytes expanded in the presence of placenta extract produced ECM, glycosaminoglycan, abundantly. Compared to chondrocyte expanded in culture medium only, chondrocytes expanded with placenta extract demonstrated higher COL2A1 expression that was biochemically comparable to primary chondrocytes. This study provides an evidence that placenta extract is helpful to expand chondrocytes during tissue cultivation, to maintain their differentiated phenotype and to promote their function. CONCLUSION: These results suggest that placenta extract during cultivation play an important role in controlling cell behaviors. Furthermore, these results provide a biologic basis for cartilage tissue engineering.

The Effect of the Initiating Time of Patient Controlled Analgesia on the Onset of Postoperative Analgesic Effect / 대한마취과학회지

BACKGROUND: Patient controlled analgesia (PCA) is now a widely accepted method of postoperative pain control. It usually begins at postanesthetic care unit, but it takes time to achieve satisfactory level. We have studied the differences in the onset of analgesic effects between starting PCA preoperatively and starting PCA postoperatively. METHODS: Forty patients for subtotal gastrectomy were randomized to two groups. In group I, we started PCA at postanesthetic care unit, in group II, PCA was begun immediately after the induction of anesthesia. We visited each patient and measured 10 cm-visual analgue scale (VAS) score at 3, 6, 9, 12 and 15 hours after the end of operation. We also measured the time taken from the end of operation to extubation. RESULTS: There were no differences in VAS score between two groups on 3 hour. But at 6, 9, and 12 hour, VAS score was significantly lower in group II (P < 0.05). On 15 hour there was no difference between two groups again. There was no significant difference in extubation time between two groups. Preemptive analgesia was not observed in group II. CONCLUSIONS: We concluded that starting PCA immediately after induction of anesthesia can achieve effective analgesia more rapidly than starting PCA at postanesthetic care unit. VAS score was lower than 3 after 12 hours after the end of operation in group II and we speculated that starting PCA 15 hours prior to operation would maximize the analgesic effect of PCA because there was approximately three hours time difference between the two groups.

A Case of Xp21 Contiguous Gene Deletion Syndrome with Hyperglycerolemia, Congenital Adrenal Hypoplasia and Duchenne Muscular Dystrophy

On Xp21 region several genes such as adrenal hypoplasia congenita(AHC) gene, glycerol kinase (GK) gene and Duchenne muscular dystrophy(DMD) gene are located contiguously. If there is a long deletion in that region, various combination of genetic defect can be occurred from one kind of genetic defect to all three kinds of genetic defect simultaneously. In case of more than two genetic defects simultaneously, we call it contiguous gene deletion syndrome. The major clinical manifestations of the Xp21 contiguous gene deletion syndrome are sum of each diseases, electrolyte imbalance and hyperpigmentation for adrenal hypoplasia congenita, psychomotor retardation, letharginess and convulsion for glycerol kinase deficiency and muscle weakness and hypotonia for Duchenne muscular dystrophy. Goals of the treatment are control of each disorders, glucocorticoid and mineralocorticoid for adrenal hypoplasia congenita, low fat diet and prevention of fasting and hypercatabolic status for glycerol kinase deficiency and physiotherapy for Duchenne muscular dystrophy. In case of hyponatremia and hyperkalemia combined with hyperpigmentation, adrenal hypoplasia congenita could be suspected. In glycerol kinase deficiency, markedly elevated glycerol excretion can be detected on urine organic acid analysis by gaschromatography with mass spectrometry. On Duchenne muscular dystrophy, creatinine kinase is markedly elevated on chemistry. We report here first Korean case of Xp21 contiguous gene deletion syndrome of adrenal hypoplasia congenita, glycerol kinase deficiency and Duchenne muscular dystrophy.

Effects of Cisapride on QTc Interval and QT Dispersion in Preterm Infants

PURPOSE: Cisapride, a prokinetic agent, is widely used in preterm infants with feeding intolerance or gastroesophageal reflux. Although cisapride is regarded as a safe drug, increased QTc interval or ventricular arrhythmia has been reported in adults and neonates. So we prospectively examined the effects of cisapride on the QTc interval and QT dispersion in preterm infants. METHODS: QTc interval and QT dispersion were determined just before and 4.9+/-1.7days after the start of the cisapride treatment in 15 preterm infants with cisapride between April 1, 1998 and August 31, 1998. RESULTS: Cisapride significantly increased QTc interval(P<0.05), and this had no correlation with birthweight or gestational age. Three(20%) of the 15 cases were found to have QTc interval above 0.450, but they were clinically asymptomatic. QT dispersion did not increase significantly. CONCLUSION: Cisapride use in preterm infants is associated with an increase in QTc interval. High dose or longterm use of cisapride in preterm infants should be used cautiously, and when used, monitoring the QTc interval should be considered.

A Case of Cyclosporine A: Induced Encephalopathy in a Child with Nephrotic Syndrome

Cyclosporine A is the most frequently used immunosuppressive agent for prevention of graft versus host disease (GVHD) and treatment of frequently relapsing nephrotic syndrome in childhood. Some adverse effects such as hepatic and renal toxicity, have been frequently encountered. But central nervous system toxicity caused by cyclosporine A is rare, and the incidence of encephalopathy among patients recieving cyclosporine A is unknown. Brain magnetic resonance imaging is an essential tool for diagnosis of cyclosporine A neurotoxicity. It typically demonstrates nonenhancing symmetric subcortical, and sometimes deep white matter changes resembling edema with posterior hemisphere predominance. We report a child with nephrotic syndrome who developed encephalopathy during cyclosporine A therapy. Based on this study, we emphasize that careful follow up of patient's neurological finding is very important to prevent serious life-threatening complications.

Tests to Differentiate Cerebrospinal Fluid from Local Anesthetics during Epidural Anesthesia / 대한마취과학회지

BACKGROUND: One of the most serious risks of epidural anesthesia is total spinal blockade from unintentional dural puncture. We evaluated the glucose test and the thiopental precipitation test to differentiate cerebrospinal fluid (CSF) from local anesthetics (LA). METHODS: (1) Experiment 1: CSF from twenty patients was serially diluted with 2% lidocaine or 0.5% bupivacaine. The ratio of CSF to LA-CSF mixture (CSF/(LA+CSF)) was from 0 to 1.0 at an interval of 0.1. We measured the glucose level of each sample with blood sugar meter. (2) Experiment 2: CSF from a hydrocephalus patient was serially diluted and its glucose level of each sample was measured in the same way as Experiment 1. We performed a urine stick test with each sample. Ten anesthetists blinded to the nature of the sample were asked to identify the results of the tests. (3) Experiment 3: Two milimeters of 2.5% thiopental was respectively mixed with local anesthetics, the amount of which was from 0.1 to 1.0 ml at an interval of 0.1 ml. Sixteen anesthetists blinded to the nature of sample were asked to identify the results of the tests. RESULTS: (1) Experiment 1: We can measure glucose level at CSF/(LA +CSF) of 0.5 in 2% lidocaine group and 0.6 in 0.5% bupivacaine group. (2) Experiment 2: We can detect glucose at lower level of CSF/(LA +CSF) by glucose meter than urine stick test (p<0.05). (3) At least 0.35 ml of 2% lidocaine and 0.29 ml of 0.5% bupivacaine was needed respectively to detect precipitation. CONCLUSION: We suggest that blood glucose meter be used instead of glucose test strip. For thiopental precipitation test, we have to adjust the amount of thiopental depending on the amount of test fluid.

Tests to Differentiate Cerebrospinal Fluid from Local Anesthetics during Epidural Anesthesia / 대한마취과학회지

BACKGROUND: One of the most serious risks of epidural anesthesia is total spinal blockade from unintentional dural puncture. We evaluated the glucose test and the thiopental precipitation test to differentiate cerebrospinal fluid (CSF) from local anesthetics (LA). METHODS: (1) Experiment 1: CSF from twenty patients was serially diluted with 2% lidocaine or 0.5% bupivacaine. The ratio of CSF to LA-CSF mixture (CSF/(LA+CSF)) was from 0 to 1.0 at an interval of 0.1. We measured the glucose level of each sample with blood sugar meter. (2) Experiment 2: CSF from a hydrocephalus patient was serially diluted and its glucose level of each sample was measured in the same way as Experiment 1. We performed a urine stick test with each sample. Ten anesthetists blinded to the nature of the sample were asked to identify the results of the tests. (3) Experiment 3: Two milimeters of 2.5% thiopental was respectively mixed with local anesthetics, the amount of which was from 0.1 to 1.0 ml at an interval of 0.1 ml. Sixteen anesthetists blinded to the nature of sample were asked to identify the results of the tests. RESULTS: (1) Experiment 1: We can measure glucose level at CSF/(LA +CSF) of 0.5 in 2% lidocaine group and 0.6 in 0.5% bupivacaine group. (2) Experiment 2: We can detect glucose at lower level of CSF/(LA +CSF) by glucose meter than urine stick test (p<0.05). (3) At least 0.35 ml of 2% lidocaine and 0.29 ml of 0.5% bupivacaine was needed respectively to detect precipitation. CONCLUSION: We suggest that blood glucose meter be used instead of glucose test strip. For thiopental precipitation test, we have to adjust the amount of thiopental depending on the amount of test fluid.

Fiberoptic Bronchoscopy via the Laryngeal Mask Airway: A case report / 대한마취과학회지

The laryngeal mask airway (LMA) has been used with increasing frequency for many purposes. It is one of its advantages that there is no need of muscle relaxants to insert the LMA. So it can be used to look into the movement of glottis during spontaneous respiration. We report a case using a fiberoptic bronchoscope via the laryngeal mask under the impression of cricopharyngeal incoordination. The patient was a 17-days-old and 3.36-kg infant. After injecting glycopyrrolate 0.05mg and propofol 10mg intravenously, a size-1 LMA was inserted. Fiberoptic bronchoscope was inserted through the LMA. We could see the movement of vocal cords normal. Also, no structural abnormality was seen in the larynx and trachea. After removal of the LMA, conventional suspension laryngoscopy was performed to examine the epiglottis and hypopharynx. We could successfully assess the movement and/or structure of vocal cord and trachea. Fiberoptic bronchoscopy via the laryngeal mask airway may be a safe and convinient method in infants.

Three Cases of Cardiac Arrythmias Associated with Intravenous Methylprednisolone Pulse Therapy

Methylprednisolone (MP) is administered by means of intravenous pulse therapy especially in the patients with focal segmental glomerulosclerosis (FSGS). There have been reports of its complications in a few increasing frequency. We experienced three cases of cardiac complications during intravenous pulse therapy. There were one case of 2 A-V block (Mobitz type I) and two cases of bradycardia and hypotension. In the former, 2 A-V block in the first case deveoloped 45 hours after MP infusion and subsided subsequently but reappeared at his EKG checked after 4 months. All of these complications resolved spontaneously. We should be awared of the fact that arrythmia resulting from MP infusion can be fetal. Therefore when IMPT are attempted, we should keep in mind of emergency life-saving preparations at bedside.